Oral Potentially Malignant

D i s o rd e r s
a, ,1 b,1
Stephanie L. Wetzel, DDS * , Jessica Wollenberg, DMD

KEYWORDS
 Premalignant  Leukoplakia  Erythroplakia  Risk factors  Epithelial dysplasia

KEY POINTS
 Oral potentially malignant disorders are epithelial lesions that may present clinically as
white (leukoplakia), red (erythroplakia), or red and white (erythroleukoplakia) patches.
 There are many factors that increase patients’ risk for developing a potentially malignant
lesion.
 A biopsy of the lesion is the gold standard to differentiate between a potentially malignant
lesion and other entities, and to diagnosis and grade epithelial dysplasia.
 After the diagnosis of a premalignant lesion is made, many patient-related and lesion-
related factors influence the type and extent of treatment of the lesion.

INTRODUCTION

Oral potentially malignant disorder (OPMD) is defined as an epithelial lesion or disorder

that has an increased risk for malignant transformation. The diagnosis of OMPD be-
gins with a clinical examination, and, when present, it is most commonly described
as a white lesion (leukoplakia) or less often as a red lesion (erythroplakia). These diag-
noses are only clinical, and a definitive diagnosis must be determined through biopsy
and histopathologic examination. Once the diagnosis of an OPMD is made, the pa-
tient’s risk factors must be evaluated to determine the risk for malignant transforma-
tion and appropriate treatment. This article reviews the clinical presentation of
OMPDs, including leukoplakia and erythroplakia; the risk factors, including tobacco,
alcohol, actinic damage, and human papilloma virus (HPV); the necessary microscopic
features to make the diagnosis; and the treatment and management of these lesions.

LEUKOPLAKIA

Oral leukoplakia is the most frequently seen potentially malignant disorder in the
oral cavity. Leukoplakias were first reported in the literature in 1877, when the

Disclosure: The authors have nothing to disclose.

a
Atlanta Oral Pathology, 2701 North Decatur Road, Decatur, GA 30022, USA; b Randolph Oral
Pathology Associates, 447 Route 10, Suite 5, Randolph, NJ 07869, USA
1
Co-first author.
* Corresponding author.
E-mail address: wetzeldds@gmail.com

Dent Clin N Am 64 (2020) 25–37

https://doi.org/10.1016/j.cden.2019.08.004 dental.theclinics.com
0011-8532/20/ª 2019 Elsevier Inc. All rights reserved.
26 Wetzel & Wollenberg

term was applied to any white lesion occurring in the oral cavity.1 Leukoplakias are
now defined as white, irreversible, and nonscrapable plaques that carry a question-
able risk to transform into cancer.1,2 More specifically, these lesions cannot be
associated with any chemical, physical, or infectious causative agents except for
tobacco, alcohol, or betel quid. In the general population the overall prevalence
is approximately 2%, with increasing prevalence for older populations.2 Leukopla-
kia has a male predilection and is usually seen in the fifth to sixth decades of life.
One prospective study on leukoplakia found the incidence rates to be 1.1 to 2.4 per
1000 patients per year for men and 0.2 to 1.3 per 1000 patients per year for
women.1
Clinically, leukoplakias can be classified according to their surface and morphologic
features. Leukoplakias can be homogeneous in appearance and have a smooth,
white, flat surface, with well-demarcated borders (Figs. 1 and 2). Nonhomogeneous
leukoplakia is classified into 3 clinical categories:
1. Speckled leukoplakia
2. Nodular leukoplakia
3. Verrucous leukoplakia

Fig. 1. (A) Granular leukoplakia featured on the left lateral border and ventral surface
of the tongue. This lesion was diagnosed via biopsy as mild epithelial dysplasia. (B)
Flat leukoplakia of the lower lip in a 50-year-old woman. Tissue biopsy showed features
of actinic cheilitis. (C) Flat and verrucous leukoplakia of the ventral and lateral
border of the tongue in an 85-year-old woman. (D) Corrugated leukoplakia of the left
lateral border of the tongue in a 30-year-old man showing features of mild epithelial
dysplasia.
 Oral Potentially Malignant Disorders 27

Fig. 2. (A) Leukoplakia with irregular borders of the floor of the mouth in a 48-year-old
woman. The lesion showed features of moderate dysplasia. (B) Flat leukoplakia of the right
ventral and lateral surfaces of the tongue in a 63-year-old man diagnosed via tissue biopsy
as moderate epithelial dysplasia. (C) Flat and verrucous leukoplakia of the lower labial mu-
cosa in a 71-year-old woman diagnosed as severe epithelial dysplasia.

Speckled leukoplakia is defined as a predominately leukoplakic lesion with areas of

erythema appearing as small, dotlike spots, or larger, irregular patches. Speckled leu-
koplakia is now termed erythroleukoplakia and is discussed in more detail later.
Nodular leukoplakia presents as an exophytic polypoid structure that is rounded
and composed of both erythematous and leukoplakic surfaces. Verrucous leukoplakia
has an elevated, proliferative, wrinkled, or corrugated surface3 Most importantly,
nonhomogeneous leukoplakia presents a higher risk for malignant transformation
than homogeneous leukoplakia. There is an overall malignant transformation rate of
1.5% to 34% for oral leukoplakic lesions. This rate can be further broken down to a
transformation rate of 3% for homogeneous lesions and 13.4% to 14.5% for nonho-
mogeneous lesions. Furthermore, 1 study showed that verrucous leukoplakia has a
transformation rate of 4.6%, with erosive lesions having a 28% risk of malignant
transformation.2
Leukoplakic lesions can occur at any site in the oral cavity. The most common sites
include the lateral border of the tongue and the floor of the mouth, followed by buccal
mucosa, hard and soft palate, and gingival/alveolar mucosa. Oral leukoplakia may be
localized to 1 site or present as diffuse and widespread oral mucosal disease.
Proliferative verrucous leukoplakia (PVL) is a rare but high-risk form of leukoplakia.
PVL most commonly presents in women more than 60 years of age who lack a clinical
history of tobacco or alcohol use. An ethnic predilection is not seen. A strong female
predilection of 4:1 has been reported with PVL. Initially, lesions of PVL present as
asymptomatic, small, well-defined white patches or plaques with or without surface
thickening. As the disease progresses, the lesions slowly enlarge and involve diffuse
surfaces along multiple sites of the oral mucosa. Lesions of PVL evolve from flat
patches to become increasingly exophytic and verrucous (Figs. 3 and 4).4,5 PVL
may involve multiple sites of the oral cavity, including the gingiva, alveolar mucosa,
tongue, palate, and buccal mucosa. The gingiva is the most commonly affected
area. Furthermore, gingival and palatal lesions are the most commonly affected sites
to undergo malignant transformation. The reported malignant transformation rate for
lesions of PVL is 63.3% to 100%.2 Even with ablative treatment, PVL has a recurrence
rate of up to 85%.6 Therefore, close surveillance of patients with PVL is of the utmost
28 Wetzel & Wollenberg

Fig. 3. PVL in an 83-year-old woman. The gingival lesion showed features of mild epithelial
dysplasia. (Courtesy of Donna Thomas Moses, DMD, Carrollton, GA).

importance. Because of the serious nature of PVL, making the correct diagnosis is crit-
ical for the health of the patient. Criteria for the diagnosis of PVL include:
1. Existence of a verrucous area
2. Involvement of more than 2 sites
3. Lesions that have increased in size and spread to other sites during the develop-
ment of the disease over at least 5 years
4. Recurrence in a previously treated area
5. Representative biopsy samples of lesional tissue have been microscopically exam-
ined, and the presence of an invasive squamous cell carcinoma has been ruled out2,3

Fig. 4. (A) PVL featuring verrucous hyperkeratosis and hyperplasia of the basal cell layer. Li-
chenoid inflammation is also identified (hematoxylin-eosin, original magnification 10). (B)
PVL with chevron keratinization and orthokeratinization with a prominent granular cell
layer (hematoxylin-eosin, original magnification 40).
 Oral Potentially Malignant Disorders 29

Despite these criteria, all lesions of PVL do not have a verrucous surface. A more
inclusive term for this condition, proliferative multifocal leukoplakia, has been
suggested.3
The differential diagnosis for leukoplakic lesions can be separated into the broad
categories of congenital, infectious, inflammatory, and mucosal injury. Common
congenital white lesions include leukoedema, which disappears after stretching
of the mucosa, and white sponge nevus (also known as Cannon disease or familial
white folded dysplasia), which typically affects the buccal mucosa bilaterally.
White lesions of infectious cause include pseudomembranous candidiasis and
oral hairy leukoplakia. However, pseudomembranous candidiasis presents as a
white membrane that can be physically wiped away leaving a raw erythematous
mucosal base. Oral hairy leukoplakia occurs as a secondary manifestation in pa-
tients with compromised immune systems and infected with the Epstein Barr virus
and is also known as human herpesvirus 4. Leukoplakic lesions of inflammatory
cause present with a lichenoid appearance and include lichen planus, lichenoid
mucositis as a result of medication side effects and contact hypersensitivities,
oral lesions of systemic lupus erythematosus, and graft-versus-host disease in pa-
tients with a history of bone marrow transplant. A detailed clinical history aids in dif-
ferentiation of inflammatory lesions from true leukoplakia. Chemical and thermal
mucosal burns, morsicatio, linea alba, and frictional keratoses all present as white
areas as a result of mucosal injury. The diagnosis of a mucosal injury can be
reached by determining the location of the injury and detailed questioning of the
patient.6

ERYTHROPLAKIA

Erythroplakia is defined as a potentially malignant disorder of the oral cavity that pre-
sents as a red patch of the oral mucosa that cannot be diagnosed as any other defin-
able lesion. The lesion cannot have traumatic, vascular, or inflammatory causes.
Erythroplakia occurs in middle-aged and elderly patients, most commonly in the sixth
and seventh decades of life. It occurs with equal frequency in both genders. Erythro-
plakia has a prevalence range from 0.02% to 0.83%, with a mean prevalence of 0.11%
in the general population.7,8 Although erythroplakia is rare, it has a much higher rate of
malignant transformation than other premalignant conditions, such as leukoplakia and
submucous fibrosis. The reported transformation rates range from 14% to 50%,8 4
times greater than the malignant transformation rates of leukoplakic lesions.9 System-
atic reviews have shown a range of 1.3% to 34% of malignant transformation in
erythroplakic lesions in the global population.5
Clinically, erythroplakia presents as an erythematous mucosal lesion that is often
smooth in appearance (Fig. 5). Erosive, granular, or nodular changes can be seen in
long-standing lesions.7 Rarely, lesions can be depressed below the mucosal surface,
alluding to their atrophic nature. Typically, these lesions are asymptomatic. Visually, a
well-defined margin can be appreciated between the lesional tissue and adjacent
normal mucosa. Most commonly, erythroplakia presents as a solitary lesion. However,
examples of multicentric lesions and lesions involving extensive portions of oral
mucosa have been reported.3,7 When palpated, erythroplakias are typically soft. Indu-
rated areas or lesions that are firm to palpation occur when malignant transformation
and invasion are present.2 The soft palate is the most common site for erythroplakia to
occur. Other common sites include ventral tongue, floor of mouth, and tonsillar pil-
lars.2 Other areas of the tongue are rarely affected.2 A diagnostic biopsy is required
to differentiate between a true erythroplakia and other pathologic entities of the oral
30 Wetzel & Wollenberg

Fig. 5. (A) A 74-year-old man with erythroplakia of the left lateral border of the tongue. (B)
Erythroplakia soft palate.

cavity. Microscopic examination of affected tissue aids in distinguishing a true eryth-

roplakia from erythematous candidiasis and lichenoid lesions, including lichen planus,
lichenoid mucositis, and oral lesions of lupus erythematosus, which can have similar
clinical appearances. In addition, a biopsy can also rule out hemangiomas and other
vascular anomalies, Kaposi sarcoma, median rhomboid glossitis, lesions secondary to
local irritation, and erythema migrans. Disorders manifesting as desquamative gingi-
vitis present as erythema of the gingiva, and include lichen planus, pemphigus vulga-
ris, and mucous membrane (cicatricial) pemphigoid.7,8
Erythroleukoplakia has a mixed red and white appearance. Unlike erythroplakia,
which is well demarcated, erythroleukoplakia often has a blended or ill-defined
margin. Clinically, erythroleukoplakia, previously termed speckled leukoplakia, pre-
sents in 2 general patterns (Fig. 6): either numerous small and irregular leukoplakic
areas within a red patch, or as an erythroplakia adjacent to a leukoplakia. Unlike leu-
koplakia and erythroplakia, patients with erythroleukoplakia often present with symp-
toms such as pain or soreness. Age, gender, and commonly affected sites for
erythroleukoplakia are the same as erythroplakia.7

RISK FACTORS
Tobacco
Smoking tobacco poses the greatest increase in risk to develop precancerous le-
sions in the oral cavity. Heavy cigarette smoking is the strongest predictor, with
1 study showing that smoking more than 20 cigarettes per day led to an increased
risk of oral leukoplakia by 2.4 to 15 times that of nonsmokers. The cumulative effect
of smoking is more important than current smoking status, which suggests that
chronic long-term tobacco smoking plays a role in premalignant changes. Benzo-
pyrene, a by-product of tobacco smoking, has been shown to be both mutagenic
and carcinogenic. In addition to cigarettes, cigar and pipe smoking produce similar
risks.10
 Oral Potentially Malignant Disorders 31

Fig. 6. (A) Erythroleukoplakia on the left lateral border of tongue in a 46-year-old man. (B)
Erythroleukoplakia of the ventral tongue in an 85-year-old woman with exophytic areas of
leukoplakia.

In some populations, the habit of placing the lit end of a cigarette into the oral cavity
is practiced, and is known as reverse smoking. The mucosal changes observed with
this practice manifest as leukoplakic plaques of the palate, mucosal nodularity, and
thickening of the mucosa surrounding salivary gland ducts. The leukoplakia associ-
ated with reverse smoking has a higher risk of malignant transformation compared
with lesions in regular cigarette smokers.3

Smokeless Tobacco
Smokeless tobacco was brought to popularity by Native Americans in North America
in the early 1900s. Smokeless tobacco saw a slight decline with the invention of cig-
arettes, but smokeless tobacco usage has continued to surge at a steady pace since.
Forms of smokeless tobacco include loose-leaf chewing tobacco, moist snuff, and dry
snuff. It is estimated that from 6 million to 22 million Americans use some form of
smokeless tobacco.
Clinically, lesions associated with smokeless tobacco use appear in the oral cavity
as inflammatory gingival and periodontal lesions, and as leukoplakia, some of which
are diagnosed as epithelial dysplasia. Squamous cell carcinoma has also been re-
ported in patients who use smokeless tobacco products. However, some studies
fail to account for risk factors such as alcohol and cigarettes. Regardless, most reports
have found clinical changes in the oral mucosa as a result of smokeless tobacco use.
The mucosal change is commonly referred to as smokeless tobacco keratosis and can
be seen at the site where the quid is placed as soon as 6 months after initial use. The
affected mucosa becomes leathery, grey-white to white, and fissured. The risk of
smokeless tobacco keratosis transforming into premalignancy or squamous cell car-
cinoma is a topic of contention. In general, most studies have found low transforma-
tion rates. High-risk sites for epithelial dysplasia seen in conjunction with smokeless
32 Wetzel & Wollenberg

tobacco use are the buccal/vestibular mucosa and the gingiva, which are the locations
where the tobacco comes into direct contact with the mucosa. One study by Boffetta
and colleagues11 estimated that up to 4% of oral cancers in men in the United States
are associated with the use of smokeless tobacco products.
Alcohol
Approximately 65% of adults in the United States consume alcoholic beverages.12
Regardless of frequency of drinking, consuming alcohol with meals, or the type of
beverage, alcohol consumption is consistently linked to an increase risk of oral prema-
lignant lesions. One study showed that ever having alcohol increases the risk devel-
oping a leukoplakic lesion 1.5 times compared with nondrinkers.12 It has also been
shown that patients who regularly drink alcohol are at increased risk of developing
recurrent disease after an initial oral precancerous lesion has been treated. The floor
of mouth and ventral-lateral tongue are the sites most closely associated with alcohol
as a risk factor, possibly because of prolonged contact with the offending substance.
Acetaldehyde, a metabolite of ethanol produced by the liver, is carcinogenic. In addi-
tion, alcohol may increase oral mucosal permeability to other carcinogens seen in as-
sociation with tobacco use, which alters epithelial proliferation. This process
exponentially increases the risk to develop oral precancerous lesions.13
Actinic Damage
Excessive sun exposure has been shown to cause actinic cheilitis, which is an
inflammatory-associated precancerous lesion of the lower lip. It presents as a white
lesion with crusting, flaking, or dryness. Blurring of the vermillion border is a common
finding seen with this condition. People who are at risk to develop actinic cheilitis
include men, fair-skinned individuals, and patients who spend extended periods
participating in outdoor activities.14
Oral Submucous Fibrosis
Oral submucous fibrosis (OSF) is associated with the long-term use of betel quid.
Typically, the quid consists of areca nut, slaked lime, tobacco, and sometimes
other additives such as spices, wrapped in a betel leaf. The quid is then placed
in the vestibule and causes a sense of euphoria for the user. OSF is most
commonly seen in patients of southeast Asian and south Asian descent.3 OSF is
a chronic disorder of the mucosa in which fibroelasticity of the affected tissue is
lost.9 OSF is characterized by palpable fibrous bands leading to limited mouth
opening and tongue rigidity. Early in the disease process, blanching of the mucosa
is seen. Rate of malignant transformation seen in submucous fibrosis is 9.13% and
patients with OSF have a risk of developing oral cancer 29.26 times that of patients
without oral submucous fibrosis.15 A predominant male predilection is seen in OSF.
Affected sites include buccal mucosa, which is the most commonly affected, fol-
lowed by tongue, lip, palate, and gingiva.15 Areca nut contains arecoline, which
stimulates fibroblasts. The slaked lime promotes penetration of arecoline into the
mucosa, leading to fibrosis of the lamina propria. The mucosal lesion most often
associated with OSF is oral leukoplakia. Increased duration of use of areca nut is
directly proportional to an increased risk of oral leukoplakia and oral squamous
cell carcinoma associated with OSF.
Human Papilloma Virus
HPV is a well-known cause of squamous cell carcinoma. HPV has been detected in
the oral cavity at a rate of up to 12% and high-risk types have shown a prevalence
 Oral Potentially Malignant Disorders 33

of up to 3%. Histopathologic evidence has been seen in some instances of oral

epithelial dysplasia. These lesions most commonly present as leukoplakia, but eryth-
roplakias and erythroleukoplakias have also been described. There is a male predilec-
tion, and the most common sites for HPV-associated oral epithelial dysplasia to occur
are the tongue and floor of mouth. The most common subtype of HPV seen in these
lesions is HPV-16, followed by HPV-33 and HPV-58. Immunohistochemical staining
for p16 serves as a surrogate marker for HPV infection. However, the standard to
confirm the presence of HPV in dysplastic oral lesions is through in situ
hybridization.5,16

MICROSCOPIC DESCRIPTION

Because oral epithelial dysplasias (OEDs) are a precursor to malignant transformation,

creating a grading system for these lesions is of utmost importance.17 Many attempts
have been made to produce a grading system for oral epithelial dysplasia that is both
reproducible and can serve as a reliable predictor of malignant transformation. How-
ever, assessing the degree of dysplasia in order to predict the prognosis and manage-
ment of OED remains challenging. The current 2017 World Health Organization (WHO)
3-tiered grading system remains the gold standard in classification of these le-
sions.18,19 Pathologists use this system to classify lesions into mild, moderate, and se-
vere epithelial dysplasia using diagnostic criteria for both architectural and cytologic
changes. Carcinoma in situ is considered synonymous with severe epithelial
dysplasia.18 The recent WHO update also mentions a binary system that was pro-
posed by Kujan and colleagues.20 This system uses similar diagnostic criteria to the
WHO 2017 system but classifies the lesions as either low-grade or high-grade dyspla-
sias, thus eliminating the in-between category of moderately dysplastic lesions. Binary
systems are used for precursor lesions at other sites throughout the body, including
the larynx, and are considered to be more reproducible and clinically relevant systems
compared with the 3-tiered approach.19–21 However, a binary system has yet to be
validated for use in the oral cavity.19,22 Regardless, the aim of both classification sys-
tems is to ensure standardization in reporting and therapeutic treatments of OED.21
Epithelial dysplasia is defined as an abnormal growth pattern that affects the normal
maturation sequence of the surface mucosa. It includes both architectural and cyto-
logic alterations, which can only be seen histologically. However, these changes
can manifest as a clinically visible lesion. The 2005 WHO diagnostic criteria classify
the lesion as mild dysplasia if alterations of the epithelial maturation sequence are
seen only in the lower one-third of the surface mucosa (Fig. 7). Moderate dysplastic
lesions have changes that encompass two-thirds of the epithelium (Fig. 8). Greater

Fig. 7. (A) Mild epithelial dysplasia showing atypical features confined to the lower one-
third of the epithelium (hematoxylin-eosin, original magnification 10). (B) Mild matura-
tional alterations include nuclear hyperchromatism, increased nuclear to cytoplasmic ratio,
and hyperplasia of the basal cell layer (hematoxylin-eosin, original magnification 40).
34 Wetzel & Wollenberg

Fig. 8. (A) Moderate epithelial dysplasia in which the atypia extends beyond the lower one-
third of the surface mucosa, but does not extend the full thickness of the epithelium (hema-
toxylin-eosin, original magnification 10). (B) Dyskeratosis, increased mitotic activity, hyper-
plasia of the basal cell layer, and nuclear hyperchromatism are identified (hematoxylin-
eosin, original magnification 40).

than two-thirds of the epithelium showing atypical features is severe dysplasia and
full-thickness changes are classified as carcinoma in situ (Fig. 9).18,23 The 2005 diag-
nostic criteria are similar to the newly updated 2017 version.23
The 2017 WHO diagnostic criteria are listed as follows:

Architectural Changes
1. Irregular epithelial stratification
2. Loss of polarity of basal cells
3. Drop-shaped rete ridges
4. Increased number of mitotic figures
5. Abnormal superficial mitosis
6. Premature keratinization in single cells (dyskeratosis)
7. Keratin pearls within rete ridges
8. Loss of epithelial cohesion

Cytologic Changes
1. Abnormal variation in nuclear size
2. Abnormal variation in nuclear shape
3. Abnormal variation in cell size
4. Abnormal variation in cell shape
5. Increased nuclear-cytoplasmic ratio
6. Atypical mitotic figures
7. Increased number and size of nucleoli

Fig. 9. (A) Severe epithelial dysplasia of the oral cavity showing dysplastic features
throughout the surface mucosa (hematoxylin-eosin, original magnification 10). (B) The
dysplastic features seen in this case of severe epithelial dysplasia include increased nuclear
to cytoplasmic ratio, drop-shaped rete ridges, and abnormal variation in nuclear size and
shape. Increased mitotic activity and irregular stratification are also seen (hematoxylin-
eosin, original magnification 40).
 Oral Potentially Malignant Disorders 35

8. Hyperchromasia
Included in the 2017 WHO Classification of Head and Neck Tumors.
Minor modifications have been made from the previously adapted 2005 WHO
classification system. These changes include elimination of basal cell hyperplasia
and the addition of loss of epithelial cohesion in the architectural change category.
Furthermore, increase in nuclear size is no longer included as a cytologic feature of
dysplasia.18,23

TREATMENT AND MANAGEMENT OF ORAL PREMALIGNANT LESIONS

Over the past 3 decades there has been little improvement in the 5-year survival rate
for patients with oral cancer.24 The current 5-year survival rate has been reported to be
approximately 57% (https://oralcancerfoundation.org/facts/). It is crucial that clini-
cians embrace the importance of early detection and treatment of premalignant
lesions.
Clinical examination and biopsy are the gold standard for the detection and diag-
nosis of oral premalignant lesions. There are many adjunctive aids available on the
market to help detect these lesions, including autofluorescence, vital staining, and
brush cytology/biopsy. These tests are minimally invasive; however, they have consid-
erable false-positive and false-negative results.24 Screening examinations for oral
cancer, as part of a comprehensive head and neck examination, are recommended
at all new patient visits, recall appointments, and emergency visits.4
The patient evaluation must begin with the collection of a detailed history from
the patient. The following information should be discussed with the patient and
documented:
 Demographic data
 History of chief complaint, including onset, progression, and symptoms
 Medical history and review of systems
 Social history, including alcohol, tobacco, and areca nut use
 Other risk factors, such as family history of cancer, and any environmental
exposures4
The clinical examination begins with an extraoral examination. Examination should
look for any head and neck asymmetry, and cutaneous lesions, followed by palpation
of the midline and lateral neck and of the major salivary glands. The intraoral examina-
tion must include visualization and palpation of all sites of the oral cavity4; this is espe-
cially important because leukoplakia is often multifocal.1 If a lesion is noted, its
characteristics, including location, size, color, surface texture, and texture and symp-
toms on palpation, must be assessed. An irritative cause of the lesion should also be
sought out. If irritation is suspected as the cause of the lesion, the cause of the irrita-
tion must be removed, and the lesion then be reevaluated in 1 to 2 months. Photo-
graphs of the lesions aid in the reevaluation process. If there is no change, or if no
irritative factor is present, a biopsy of the lesion is mandatory.1 Histopathology is
the most important factor in the diagnosis of oral premalignant lesions.4
Risk factors associated with an increased risk of malignant transformation of a pre-
malignant lesion must also be assessed. Factors that increase risk of malignant trans-
formation that are patient related include female gender, patients 45 years of age or
older, and nonsmoking status (so-called idiopathic leukoplakia).5 Factors associated
with the premalignant lesion that increase the risk of malignant transformation include
site (floor of the mouth, ventral-lateral tongue, soft palate, and retromolar pad), size
36 Wetzel & Wollenberg

(>200 mm2), clinical appearance (nonhomogeneous lesions, presence of multiple le-

sions), and higher grade of dysplasia.4,25
Treatment and management of patients with oral precancerous lesions are deter-
mined by evaluating their risk for malignant progression. The most important factors
used to stratify patients include the clinical factors discussed earlier and histologic
grade. Treatment of low-risk lesions that show mild dysplasia on biopsy may include
habit cessation, surveillance, or surgical intervention.4 One study has shown that there
was a 44% rate of clinical improvement in lesions of mild dysplasia in smokers who
discontinued tobacco use. The decision whether to treat a lesion of mild dysplasia
should take into account the extent of the lesion, whether the lesion is multifocal,
risk factors, and the patient’s preference.1
High-risk lesions, and lesions that show moderate or severe dysplasia on biopsy,
should be treated. The goal of treatment is to remove all the epithelium affected by
the oral precancerous lesion.1 Surgical removal with cold-blade scalpel excision or
electrocautery excision significantly reduces the risk of transformation of the lesion.
The lesion may also be treated by laser ablation. Most commonly a CO2 laser is
used to vaporize the affected epithelium. Regardless of how the lesion is to be treated,
a 1-mm to 2-mm margin of normal mucosa is recommended.4
After appropriate treatment of an oral precancerous lesion, close, long-term surveil-
lance is imperative. The interval between reevaluation visits varies depending on the
patient’s risk factors. It has been recommended that a complete extraoral and intrao-
ral examination be done every 3 to 6 months. If any changes or new lesions are noted,
a biopsy is required.1 Regardless of the patient’s risk factors and previous treatments,
lifelong monitoring is suggested.4

SUMMARY

Identifying OPMDs in the oral cavity begins with thorough clinical examination of the
soft tissue in the oral cavity and assessment of the patient’s risk factors. Presence
of an OPMD is confirmed via biopsy and microscopic examination of the lesional tis-
sue. The treatment of OPMDs depends on the definitive diagnosis rendered from the
biopsy specimen. Low-risk epithelial dysplasias should be closely monitored and bio-
psied when any changes to the lesion occur. High-risk dysplastic lesions need to be
excised surgically with close and long-term follow-up of the patient. Adherence to
this protocol for OPMD remains the standard of care in prevention of transformation
to malignancy.

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